The Red Devils recorded a 4-2 victory over Aston Villa to advance to this stage of the competition, while Burnley have beaten both Shrewsbury Town and Crawley Town in this season's tournament.
Match preview
Man United have not been in competitive action since November 13, when they recorded a 2-1 victory over Fulham in the Premier League, with Alejandro Garnacho scoring the winner in the 93rd minute.
The result left the Red Devils in fifth spot in the Premier League table, three points behind fourth-placed Tottenham Hotspur, with a game in hand on the North London club; Erik ten Hag's side will be back in league action against Nottingham Forest on December 27, but their immediate focus is on the EFL Cup.
Man United recorded a 4-2 victory over Aston Villa in the last round of the competition, and they are bidding to win the EFL Cup for the fifth time in their history this season.
The 20-time English champions last lifted the trophy in 2017 by beating Southampton, and there is no question that Ten Hag will be taking this competition seriously, as he bids to deliver silverware in his first season.
The Red Devils recorded a 3-1 victory over Burnley when the two teams locked horns in the Premier League at Old Trafford last season, but the points were shared in a 1-1 draw at Turf Moor back in February.
Burnley resumed their campaign on December 11 against Queens Park Rangers, recording a 3-0 victory over the capital outfit, before running out 3-1 winners over Middlesbrough on Saturday.
Vincent Kompany's side are top of the Championship, boasting 47 points from their opening 23 matches, which has left them six points clear of second-placed Sheffield United.
Burnley have had to win two matches to reach this stage of the EFL Cup, recording a 1-0 victory over Shrewsbury Town on August 23 before beating Crawley Town 3-1 last time out.
The League Cup is not a priority competition for the Clarets this season, with the team's main focus being the Championship, as they bid to secure a return to the Premier League for the 2023-24 campaign.
Burnley have actually never won the League Cup, but they lifted the FA Cup in 1913-14, and a victory over Man United on Wednesday would certainly leave them full of confidence heading into the final eight.
Manchester United EFL Cup form:
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Burnley EFL Cup form:
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Team News
Man United will again be without the services of Axel Tuanzebe through injury, while Diogo Dalot is a doubt with the hamstring problem that he picked up while representing Portugal at the World Cup.
Jadon Sancho is also a major doubt, having recently been on an individual fitness programme, with the Englishman not travelling to Spain for the team's winter training camp, which included matches against Cadiz and Real Betis.
Raphael Varane and Lisandro Martinez are definitely out of this match due to their involvement in the World Cup final, but there are expected to be players who featured in the competition that start on Wednesday.
One of those could be club captain Harry Maguire, who might be rushed back due to Ten Hag's lack of options in that area of the field, while Tyrell Malacia and Christian Eriksen could also feature.
Aaron Wan-Bissaka might get the nod at right-back, while Anthony Elanga, Donny van de Beek, Garnacho and Anthony Martial could also be in the XI.
As for Burnley, Scott Twine picked up an injury while appearing as a late substitute against Middlesbrough, so the midfielder will not be available for selection at Old Trafford.
Connor Roberts was sent off against Boro, meanwhile, which will rule him out of this game through suspension.
Kompany will make changes from the side that started in the league at the weekend, with Ashley Barnes, Charlie Taylor, Bailey Peacock-Farrell among those set to come into the XI.
Manchester United possible starting lineup:
De Gea; Wan-Bissaka, Maguire, Lindelof, Malacia; McTominay, Eriksen; Elanga, Van de Beek, Garnacho; Martial
Burnley possible starting lineup:
Peacock-Farrell; Taylor, Harwood-Bellis, Beyer, Maatsen; Cullen, Bastien; Manuel, Brownhill, Churlinov; Barnes
We say: Manchester United 2-1 Burnley
Burnley will fancy their chances of causing an upset here considering that Man United will be missing a number of important players, and we are expecting a very close match. Ten Hag will still be able to send a high-quality XI onto the field, though, and we are backing the home side to secure a narrow win.